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Discogenic low back pain (DLBP) is extremely common and costly. Effective treatments are lacking due to DLBP's unknown pathogenesis. Currently, there are no in vivo mouse models of DLBP, which restricts research in this field. The aim of this study was to establish a reliable DLBP model in mouse that captures the pathological changes in the disc and allows longitudinal pain testing. The model was generated by puncturing the mouse lumbar discs (L4/5, L5/6, and L6/S1) and removing the nucleus pulposus using a microscalpel under the microscope. Histology, molecular pathways, and pain-related behaviors were examined. Over 12 weeks post-surgery, animals displayed the mechanical, heat, and cold hyperalgesia along with decreased burrowing and rearing. Histology showed progressive disc degeneration with loss of disc height, nucleus pulposus reduction, proteoglycan depletion, and annular fibrotic disorganization. Immunohistochemistry revealed a substantial increase in inflammatory mediators at 2 and 4 weeks. Nerve growth factor was upregulated from 2 weeks to the end of the experiment. Nerve fiber ingrowth was induced in the injured discs after 4 weeks. Disc-puncture also produced an upregulation of neuropeptides in dorsal root ganglia neurons and an activation of glial cells in the spinal cord dorsal horn. These findings indicate that the cellular and structural changes in discs, as well as peripheral and central nervous system plasticity, paralleled persistent, and robust behavioral pain responses. Therefore, this mouse DLBP model could be used to investigate mechanisms underlying discogenic pain, thereby facilitating effective drug screening and development of treatments for DLBP.

OBJECTIVE: To assess changes in energy sensing and cell survival pathways both during bupivacaine-induced cardiac pharmacotoxicity and during the accelerated recovery caused by lipid-emulsion. METHODS: Male Sprague-Dawley rats were anesthetized and instrumented to monitor arterial pressures, carotid flows and to deliver drugs to both jugular veins. Animals were separated into 4-conditions: no treatment (control), 10mL/kg lipid emulsion (30% Intralipid, Frensius Kabi, Uppsala, Sweden) over 1 minute, 10mg/kg Bupivacaine over 20s, or 10mL/kg Bupivacaine followed 10 seconds later by 10mL/kg lipid emulsion. Animals were sacrificed at four time-points 0 minutes (for control), 1, 5 & 10 minutes following infusions. Hearts were flash-frozen and proteins extracted in an anti-protease, anti-phosphatase buffer. Following protein quantified for equal loading, the samples were run on a 4-15% Bis-Tris gel, transferred to nitrocellulose paper, stained with phosphorylation-site-specific antibodies in the AMPK and Akt...